Conspectus
Boron Lewis acid catalysis has a long history
and has become one
of the most powerful methods for organic synthesis. In addition to
achiral boron catalysts such as BX3 (X = F, Cl, Br) and
B(C6F5)3, chiral boron catalysts
are also significant synthetic tools used by organic chemists in academic
laboratories and industry. Since first reported by Corey et al. in
2002 (J. Am. Chem. Soc.20021243808), the chiral oxazaborolidinium ion
(COBI), an activated form of proline-derived oxazaborolidine, has
been used as a strong Lewis acid catalyst. Although the early examples
of asymmetric synthesis through COBI-catalyzed nucleophilic 1,2- or
1,4-carbonyl additions were reported in 2004–2006, Diels–Alder
and cycloaddition reactions of various carbonyl compounds were mostly
developed over the next several years to afford enantioenriched cyclized
products. The power of COBI in catalyzing carbonyl 1,2- or 1,4-addition
reactions triggered our interest in developing asymmetric synthetic
methodologies to generate versatile enantiomerically enriched compounds.
In this Account, we summarize our recent studies on COBI-catalyzed
asymmetric nucleophilic carbonyl addition and tandem reactions. Logical
mechanistic explanations of asymmetric COBI catalysis are also discussed.
The proton-activated COBI catalyst, which can activate various
carbonyl compounds such as aldehydes, ketones, acroleins, and enones
through Lewis acid–base interactions and synergistic hydrogen
bonds, facilitates asymmetric 1,2- or 1,4-carbonyl additions of nucleophiles.
Nucleophiles bearing trialkylsilyl groups successfully reacted with
aromatic, aliphatic, and α,β-unsaturated aldehydes through
1,2-addition reactions resulting in chiral β-hydroxy esters.
In addition, efficient asymmetric hydrosilylation of ketones was achieved
with a TfOH-activated COBI catalyst. Optically active β-keto
esters and all-carbon quaternary aldehydes were synthesized successfully
through asymmetric 1,2-addition of diazo compounds and tandem H- or
C-migration, respectively. In some cases, epoxide products were obtained
as side products via the Darzens reaction pathway. Solvent and π–π
interactions played important roles in favoring C-migration over H-migration.
Nucleophilic 1,4-addition of diazo compounds and chemoselective ring-closure
afforded an efficient approach to cyclopropanes, and their tandem
rearrangements provided four- and seven-membered cyclic compounds
with excellent stereoselectivity. After a Michael addition of diazo
compounds, the selective β-hydride shift pathway afforded the
β-substituted cyclic enones with high diastereo- and enantioselectivity.
The presence of π-bond(s) in the substituents at the α-position
of the diazo compound hindered the β-hydride shift pathway and,
as a result, favored the cyclopropanation pathway. While there still
remain challenges to be overcome, these results further understanding
of COBI catalysis and open a window for future development of new
asymmetric synthetic methods using carbonyl addition and tandem reactions.